The pathogenesis of AIDS will be studied using a molecularly cloned, acutely pathogenic, simian immunodeficiency virus, SIVsmmPBj14. A collaboration with a highly-regarded primatologist at the University of Alabama at Birmingham (Dr. P. Fultz) has been established and experiments are proposed to determine the pathobiologic significance of mutations in cis-acting sequences which regulates viral transcription. Other studies focus on improving gene therapeutic approaches to HIV treatment. These experiments involve the characterization and analysis of cis-acting DNA elements which regulate the DNA replication of a ubiquitous human virus, human herpesvirus 6 (HHV-6). Ultimately, these studies are expected to result in the development of gene delivery vectors or artificial mini- chromosomes" based on this T-lymphotropic herpesvirus.